Interleukin-2 (IL-2) is a critical cytokine for T cell peripheral tolerance and immunity. Here, we review how IL-2 interaction with the high-affinity IL-2 receptor (IL-2R) supports the development and homeostasis of regulatory T cells and contributes to the differentiation of helper, cytotoxic, and memory T cells. A critical element for each T cell population is the expression of CD25 (Il2rα), which heightens the receptor affinity for IL-2. Signaling through the high-affinity IL-2R also reinvigorates CD8+ exhausted T (Tex) cells in response to checkpoint blockade. We consider the molecular underpinnings reflecting how IL-2R signaling impacts these various T cell subsets and the implications for enhancing IL-2-dependent immunotherapy of autoimmunity, other inflammatory disorders, and cancer.
Keywords: T cell exhaustion; autoimmunity; cancer immunotherapy; cytokine; cytokine signaling; effector T cells; immunotherapy; interleukin-2; interleukin-2 receptor; memory T cells; regulatory T cells.
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